Nanodelivery of arsenic fights lymphoma while preserving fertility

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Packaging crystalline arsenic particles in a bubble of fat helps deliver the drug into lymphoma cells without damaging ovarian tissue, follicles, or eggs, recent research has demonstrated.

The drug delivery system, known as a nanobin, consists of the fat bubble, or liposome, densely packed with half a million molecules of arsenic trioxide. Arsenic trioxide is a potent agent for the treatment of hematologic malignancies.

Because the liposome is hundreds of times smaller than the average cell, it can easily slip into tumor-nourishing blood vessels. According to a statement from Northwestern University in Chicago, Illinois, where the nanobin was developed, acid in the cancer cells triggers the release of the liposome's drug cargo so that a highly effective dose of arsenic trioxide is delivered where it is needed.

When Teresa K. Woodruff, chief of fertility preservation at Northwestern University Feinberg School of Medicine, and her husband Thomas O'Halloran, director of the Chemistry and Life Processes Institute at Northwestern, developed and tested the nanobin, they found that the arsenic trioxide had significantly better activity in that form than did the free drug in a mouse model of lymphoma.

The coprincipal investigators and their fellow researchers also developed an in vitro test of ovarian follicle function that predicts in vivo ovarian toxicity of therapeutic agents. They found that the nanotherapeutic arsenic trioxide was not only more active against lymphoma but also less deleterious to ovarian function than was the parent drug.

“The drug was designed to maximize its effectiveness but reduce fertotoxicity,” explained O'Halloran in the Northwestern statement. “Many cancer drugs cause sterilization; that's why the reproductive tract is really important to focus on in the new stages of drug design. Other body systems get better when people stop taking the drug, but fertility you can't recover.”

The scientists concluded in PLOS One that their in vitro assay allows for rapid evaluation of both established and experimental anticancer drugs on ovarian reserve and can inform the selection of effective and fertility-sparing treatment regimens for women of reproductive age who have cancer.

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